Objective To demonstrate that the development of progressive osteopenia in ovariectomized rhesus monkeys can be prevented by treatment with the bisphosphonate compound CGP 42,446. Osteoporosis, a condition of reduced bone strength leading to an increased risk of fractures, is one of the most common conditions seen with advancing age. The non-human primate is the best model in which to study potential therapies for this condition as bone remodeling at both cancellous and cortical sites is extremely similar to humans (unlike lower species such as the rat). As potential therapeutic agents may have beneficial effects on cancellous sites but deleterious effects on cortical sites, this similarity permits the documentation of safety and efficacy of revent postmenopausal bone loss and may reduce fracture risk. CGP 42,446 is the most potent bisphosphonate yet identified, as such, it may be a significant therapeutic addition for the prevention and treatment of osteoporosis. This study will be the most comprehensive assessment of estrogen depletion bone loss and the effect of a bisphosphonate compound on this loss in the rhesus monkey. These effects will be evaluated by detailed biochemical analysis, fluorochrome labeled bone histomorphometry and bone biomechanical testing. In addition, we have adapted bone densitometry to evaluate the sites of clinical relevance in the human (spine, hip and wrist). Keywords Osteoporosis, bisphosphonate, estrogen-depletion, bone density, bone strength